Membrane chromatography is a relatively new purification technique which involves the use of a stack of synthetic membranes as chromatographic media. Membrane chromatography is emerging as a fast and cost-effective alternative to resin-based column chromatography.
One attractive feature of membrane chromatography is the speed of separation. The predominantly convection-based transport of target bio-molecules to and from their binding sites on a membrane, as opposed to the largely diffusion-limited mass transport of these molecules within the resin bed makes membrane chromatography significantly faster. Membrane chromatography could therefore be faster by more than one order of magnitude, a factor which contributes towards higher productivity and decrease in product degradation by proteolysis, denaturation and aggregation.
The predominance of convection-based transport of target bio-molecules also makes it easier to model membrane chromatography. Also, in membrane chromatography, the efficiency of binding of even large solutes such as monoclonal antibodies is relatively independent of the superficial velocity. This offers significant flexibility in process design. Other advantages include lower buffer usage and pressure drops, and the absence of problems such as channeling and fracturing of resin beds. Moreover, the disposable nature of membrane devices eliminates the need for cleaning and validation steps, and thereby contributes toward practicality and ease of use.
The efficiency of membrane chromatography is critically dependent on the fluid flow distribution within the membrane device. Membrane chromatography devices are commonly available in two formats: a) stacked discs, and b) radial flow. Both types of devices suffer from poor flow distribution which can lead to shallow breakthrough and consequently poor binding capacity utilization.
Existing stacked disc devices often resemble syringe-type micro-filters that are relatively easy to fabricate and are used for preliminary process development work. Stacked disks typically have large radial to axial dimension ratios. The feed enters at a location corresponding to the center of the first disk, while the flow-through is collected from the center of the last membrane in the stack. Consequently, the central region of the stack gets saturated with solute much earlier than the peripheral regions leading to poor breakthrough binding capacities. Radial flow devices have complicated design, and are used for large-scale purification. They have large dead volumes on both feed and permeate side, and a large central core for supporting the membrane, and therefore extremely poor device volume utilization.